Bottom Line:
The median proportion of extrapulmonary TB cases was significantly increased among zTB in comparison with data from registries of Europe and USA, reporting mainly MtTB cases (47% versus 22% in Europe, 73% versus 30% in the USA).Our findings, based on global data, confirm the widely suggested association between zTB and extrapulmonary disease.Different disability weights for zTB and MtTB should be considered and we recommend separate burden estimates for the two diseases.

ABSTRACTTuberculosis (TB) is one of the most devastating infectious diseases worldwide. Whilst global burden estimates for M. tuberculosis infection (MtTB) are well established, accurate data on the contribution of zoonotic TB (zTB) caused by M. bovis or M. caprae to human TB are scarce. The association of M. bovis infection with extrapulmonary tuberculosis has been suggested repeatedly, though there is little scientific evidence available to support this relationship. The present study aimed to determine globally the occurrence of extrapulmonary TB and the primary site (i.e. primary body location affected) of zTB in comparison with MtTB, based on previously published reports. A systematic literature review was conducted in 32 different bibliographic databases, selecting reports on zTB written in English, French, German, Spanish or Portuguese. Data from 27 reports from Africa, America, Europe and the Western Pacific Region were extracted for analyses. Low income countries, in Africa and South-East Asia, were highly underrepresented in the dataset. The median proportion of extrapulmonary TB cases was significantly increased among zTB in comparison with data from registries of Europe and USA, reporting mainly MtTB cases (47% versus 22% in Europe, 73% versus 30% in the USA). These findings were confirmed by analyses of eight studies reporting on the proportions of extrapulmonary TB in comparable populations of zTB and MtTB cases (median 63% versus 22%). Also, disparities of primary sites of extrapulmonary TB between zTB and MtTB were detected. Our findings, based on global data, confirm the widely suggested association between zTB and extrapulmonary disease. Different disability weights for zTB and MtTB should be considered and we recommend separate burden estimates for the two diseases.

pntd-0002399-g003: Proportion of extrapulmonary sites of TB per WHO region (n = the number of studies per region).The circle diameter is proportional to the number of patients included in the study. The diamond represents the median proportion of the respective region. *significant differences exists only between the WHO regions America and Western Pacific (two sample Wilcoxon signed rank test, n = 10, W = 21, p = 0.017).

Mentions:
Information on the proportion of extrapulmonary TB cases among all zTB patients was presented in 26 of the studies included (Table S4, footnote 1) and varied substantially between and within WHO region (Table 1, Figure 3). The region with the highest median value of extrapulmonary TB cases (73%, range 46–95%) was the Americas. Two studies from USA, which reported high proportions of extrapulmonary TB (95% and 74%, respectively), were conducted in specific populations. The first report included children only (0–15 years) [18] and the second was related to a food-borne outbreak caused by unpasteurized cheese, where a high proportions of extrapulmonary TB is expected [21]. Nevertheless, two other studies conducted in representative populations from the State of Michigan and the whole of the USA covering a period of 10 years, also reported proportions of 73% and 74% [22], [23]. According to the estimates in the studies conducted in Europe, the median proportion of extrapulmonary TB was 47% (21–99%). The only report from Africa presented a low proportion of extrapulmonary TB (11%) [15]. The three studies included from the Western Pacific region reported proportions of extrapulmonary TB from 13–43% with a median of 28% [11], [24], [25].

pntd-0002399-g003: Proportion of extrapulmonary sites of TB per WHO region (n = the number of studies per region).The circle diameter is proportional to the number of patients included in the study. The diamond represents the median proportion of the respective region. *significant differences exists only between the WHO regions America and Western Pacific (two sample Wilcoxon signed rank test, n = 10, W = 21, p = 0.017).

Mentions:
Information on the proportion of extrapulmonary TB cases among all zTB patients was presented in 26 of the studies included (Table S4, footnote 1) and varied substantially between and within WHO region (Table 1, Figure 3). The region with the highest median value of extrapulmonary TB cases (73%, range 46–95%) was the Americas. Two studies from USA, which reported high proportions of extrapulmonary TB (95% and 74%, respectively), were conducted in specific populations. The first report included children only (0–15 years) [18] and the second was related to a food-borne outbreak caused by unpasteurized cheese, where a high proportions of extrapulmonary TB is expected [21]. Nevertheless, two other studies conducted in representative populations from the State of Michigan and the whole of the USA covering a period of 10 years, also reported proportions of 73% and 74% [22], [23]. According to the estimates in the studies conducted in Europe, the median proportion of extrapulmonary TB was 47% (21–99%). The only report from Africa presented a low proportion of extrapulmonary TB (11%) [15]. The three studies included from the Western Pacific region reported proportions of extrapulmonary TB from 13–43% with a median of 28% [11], [24], [25].

Bottom Line:
The median proportion of extrapulmonary TB cases was significantly increased among zTB in comparison with data from registries of Europe and USA, reporting mainly MtTB cases (47% versus 22% in Europe, 73% versus 30% in the USA).Our findings, based on global data, confirm the widely suggested association between zTB and extrapulmonary disease.Different disability weights for zTB and MtTB should be considered and we recommend separate burden estimates for the two diseases.

ABSTRACTTuberculosis (TB) is one of the most devastating infectious diseases worldwide. Whilst global burden estimates for M. tuberculosis infection (MtTB) are well established, accurate data on the contribution of zoonotic TB (zTB) caused by M. bovis or M. caprae to human TB are scarce. The association of M. bovis infection with extrapulmonary tuberculosis has been suggested repeatedly, though there is little scientific evidence available to support this relationship. The present study aimed to determine globally the occurrence of extrapulmonary TB and the primary site (i.e. primary body location affected) of zTB in comparison with MtTB, based on previously published reports. A systematic literature review was conducted in 32 different bibliographic databases, selecting reports on zTB written in English, French, German, Spanish or Portuguese. Data from 27 reports from Africa, America, Europe and the Western Pacific Region were extracted for analyses. Low income countries, in Africa and South-East Asia, were highly underrepresented in the dataset. The median proportion of extrapulmonary TB cases was significantly increased among zTB in comparison with data from registries of Europe and USA, reporting mainly MtTB cases (47% versus 22% in Europe, 73% versus 30% in the USA). These findings were confirmed by analyses of eight studies reporting on the proportions of extrapulmonary TB in comparable populations of zTB and MtTB cases (median 63% versus 22%). Also, disparities of primary sites of extrapulmonary TB between zTB and MtTB were detected. Our findings, based on global data, confirm the widely suggested association between zTB and extrapulmonary disease. Different disability weights for zTB and MtTB should be considered and we recommend separate burden estimates for the two diseases.